Proposed Indications: For use inunrelated donor hematopoietic progenitor cell transplantation procedures in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.

Final formulation: Each unit of AlloCORD contains a minimum of 5 x 108 total nucleated cells (TNC) with a minimum of 1.25 x 106 viable CD34+ cells, suspended in 10% dimethyl sulfoxide (DMSO), and 1% dextran 40, at the time of cryopreservation

Mid-Cycle Summary
The applicant applied for licensure of its cord blood product indicated for use inunrelated donor hematopoietic progenitor cell transplantation procedures in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment. The applicant referred to the COBLT data and the docket data to support the efficacy of its product.The applicant submitted a dataset of 1130 cord blood recipients (1055 subjects with single unit infusions and 75 subjects with more than one unit infusions) to support the safety of its product.These units of the cord blood were collected from 33 collection sites in the States of Missouri, Illinois and Kansas from 1996 to 2011.The following summarizes our joint preliminary data analyses from the raw dataset provided by the applicant.

1. The FDA data analyses are based on an incomplete dataset of patients who received a single unit of the product.Missing data occur in various degrees for the different variables; this is largely due to the retrospective and passive nature of data collection.In addition, multiple miscodings and inconsistencies within the dataset have been identified.

2. The main age category consists of pediatric patients (1 month to < 18 years) - 52% and young adults (18 to <65) - 44%.Neonates (1 month or younger) and geriatric patients (≥ 65) are represented in a small proportion (3.5%)(Table 1).

3. 82.9% of cord blood units are given to patients with hematological malignancies, and 7.1% of cord blood units are given to patients with immunodeficiency. Other categories include metabolic disorders, bone marrow failure, hemoglobinopathy and autoimmune diseases (Table 1).

4. Among the 644 recipients with information on the number of total nuclear cells infused, the median dose is 4.4 x 107 /kg (Table 1).

6. Hematopoietic recovery of neutrophil and platelet are calculated from this retrospective dataset. They are consistent with those from the COBLT study and the Docket (Table 3).

7. Overall reported death rate is 51% (392/764). The rate is compatible with docket data, as is the rate of death < 100 days post-transplant. The main causes of death include primary diseases, infection, pulmonary etiologies, GVHD, graft failure, and organ failure.Death due to graft failure or GVHD accounts for 5.1% and 4.6% of deaths, respectively (Table 4).

9. Infusion reactions occurred in 18% of 453 patients. The most common reaction is hypertension, followed by other relatively common ones, including nausea, vomiting, bradycardia, headache, and chest pain (Table 6). 10.The preliminary analyses of the safety outcomes areroughly compatible with Docket/public data. Therefore, the current assessment is that a post-market study (REMS or PMR) may not be necessary.However, the final review may suggest otherwise.

Table 1. Demographic Characteristics

Category

St. Louis

Docket

Number of patients

N=1055 (%)

N=1572 (%)

Age

Median (range)

16 yrs (25 d-73 yrs)

6 yrs (<1-66 yrs)

< 1 month

2 (0.19)

1 month – < 18 years

549 (52)

1296 (82)

18 - < 65 years

469 (44)

276 (17.7)

≥ 65 years

35 (3.3)

Gender

Male

601 (57)

Female

454 (43)

Race/Ethnicity

Caucasian African American Hispanic Asian American Indian Other / Unknown